Common cancer-related symptoms among GP patients Opportunistic screening in primary health care

Objective - To study the occurrence of symptoms related to the five most common forms of cancer among patients regularly visiting primary care. To estimate the proportion of symptoms needing GP examination, and the number of tumours thus diagnosed. Design - Patients with some form of non-malignant chronic disease received a letter with information about cancer-related symptoms along with an invitation to regular check-up. The letter described the most common symptoms of breast, colorectal, lung, prostate and skin cancers. Setting - 12 health centres in Kalmar County, Sweden. Subjects - 5200 patients aged over 40 years. Results - One patient in 13 reported cancer-related symptoms to the GP. Women reported more symptoms than men, and almost half of them had had symptoms at previous check-ups. The GP was able to explain 7 out of 10 patients' symptoms directly. When other symptoms were examined, 8 cancers were diagnosed as well as 6 pre-malignant tumours, corresponding to 3 tumour diagnoses per 1000 check-ups. Conclusion ? While attending regular check-ups, patients may not report symptoms which cause anxiety and sometimes indicate serious diseases. It is possible to widen the perspective and link both primary and secondary prevention of certain cancers to the check-up.     

Secretory and serum immunoglobulin class-specific antibodies to poliovirus after vaccination

Immune responses in serum and saliva were studied in Pakistani children by enzyme-linked immunosorbent assay after natural exposure to poliovirus and vaccination with live or inactivated poliovirus vaccines. Swedish children unexposed to wild poliovirus who had almost 100% vaccination coverage with inactivated vaccine at 8, 9, and 18 months and at 5 years of age were analyzed for comparison. Natural exposure induced secretory IgA (SIgA) antibodies to poliovirus in the saliva of Pakistani infants at one month of age that reached adult levels at six months. No difference in levels of salivary antibody at eight months was observed between groups vaccinated with either live or inactivated vaccines. Vaccination with live or inactivated vaccine starting at 2 or 3 months of age resulted in high titers of IgG antibody to poliovirus in serum, the highest of which occurred after four doses of live vaccine. In Sweden, an increase of antibody in serum was observed after the third vaccination. IgA antibodies continued to increase subsequently, whereas IgG antibodies reached a plateau. The SIgA response in saliva initially appeared on the third vaccination, with a significant increase after the fourth. Repeated vaccination with inactivated poliovirus vaccine induces specific SIgA antibodies. Adults all had SIgA antibodies to poliovirus in saliva.     

Acute low-back-pain patients exhibit a fourfold increase in sick leave for other disorders: a case-control study.

One hundred eighty patients with acute low-back pain (LBP) were compared to 608 age- and sex-matched controls with regard to somatic and personality characteristics. The low-back-pain group had a fourfold increase (median) in sick-leave episodes for reasons other than spinal morbidity during the preceding 2 years. In the same period, the median number of episodes of sick leave for LBP was 1 in the patients and 0 in the controls. The mean number of days off for other reasons was 34 (median = 20.5) in the patients compared to 9 (median = 0) in the controls, and days off for LBP were 20 (median = 5) and 5 (median = 0), respectively. Analysis of other factors than those directly related to LBP disclosed significant differences in marital status and smoking habits between patients and controls. Furthermore, LBP patients estimated their work to be physically heavier. We conclude that medical intervention should focus not only on the spine, but also on a wide range of other aspects of the patient's situation. Even in the acute phase of LBP, the previous sick-leave records should be analyzed to provide adequate measures to prevent future sick leaves. Presently, the sociomedical costs for a subset of the population who repeatedly seek help for LBP are significantly higher than those for the non-LBP population.     

Predictive Value of Four Kallikrein Markers for Pathologically Insignificant Compared With Aggressive Prostate Cancer in Radical Prostatectomy Specimens: Results From the European Randomized Study of Screening for Prostate Cancer Section Rotterdam

Background

Treatment decisions can be difficult in men with low-risk prostate cancer (PCa).

Objective

To evaluate the ability of a panel of four kallikrein markers in blood—total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2—to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries.

Design, setting, and participants

The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA ≥3.0 ng/ml and were treated with RP between 1994 and 2004.

Outcome measurements and statistical analysis

We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3–T4, extracapsular extension, tumor volume >0.5 cm³, or any Gleason grade ≥4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood.

Results and limitations

A total of 261 patients (67%) had significant disease on pathologic evaluation of the RP specimen. While the clinical model had good accuracy in predicting aggressive disease, reflected in a corrected AUC of 0.81, the four kallikrein markers enhanced the base model, with an AUC of 0.84 (p < 0.0005). The model retained its ability in patients with low-risk and very-low-risk disease and in comparison with the Steyerberg nomogram, a published prediction model. Clinical application of the model incorporating the kallikrein markers would reduce rates of surgery by 135 of 1000 patients overall and 110 of 334 patients with pathologically insignificant disease. A limitation of the present study is that clinicians may be hesitant to make recommendations against active treatment on the basis of a statistical model.

Conclusions

Our study provided proof of principle that predictions based on levels of four kallikrein markers in blood distinguish between pathologically insignificant and aggressive disease after RP with good accuracy. In the future, clinical use of the model could potentially reduce rates of immediate unnecessary active treatment.     

Conservative treatment in patients sick-listed for acute low-back pain: a prospective randomised study with 12 months’ follow-up

We evaluated three different conservative treatment methods for acute low-back pain patients in groups following a manual therapy programme, an intensive training programme, or a general practitioner programme, the latter serving as the control group. Patients aged 19–64 years on sick leave for low-back pain with or without sciatica were included in a prospective randomised study evaluating outcomes such as impairment, pain, functional disability, socio-economic disability and satisfaction with the treatment or explanations. Evaluation by unbiased observers was performed at 1, 3 and 12 months. The three treatment groups were comparable at baseline. With regard to satisfaction, the patients in the manual therapy programme and those in the intensive training programme were more satisfied with the treatment than those in the general practitioner programme at all follow-ups. With regard to the explanations of current low-back pain episodes, the patients in the manual therapy programme were more satisfied than those in the general practitioner programme at all follow-ups. The manual therapy programme group were also more satisfied with the explanations than those in the intensive training programme at the 1-month follow-up. However, no differences were revealed between the groups with respect to outcomes on measures of impairment, pain, functional disability or socio-economic disability. All three study groups showed rapid improvement. After 1 month a significant improvement was noted in all outcome values compared with the values on entry to the study. Within the limitations discussed in our study, it is concluded that (1) patients sick listed with acute low-back pain, with or without sciatica, will be significantly improved after 1 month regardless of conservative treatment programme; (2) they will be more satisfied with the treatment if they are referred to a manual treatment programme or a training treatment programme; (3) they will be more satisfied with the explanations of the acute low-back problem if they are referred to one of the above groups, especially the manual treatment group; (4) they will not show any other differences with respect to subjective and objective variables, either at short-term or at long-term follow-ups. Received: 6 October 1997 Revised: 10 March 1998 Accepted: 27 April 1998     

Cemented tibial component fixation performs better than cementless fixation: a randomized radiostereometric study comparing porous-coated, hydroxyapatite-coated and cemented tibial components over 5 years

Background The question whether the tibial component of a total knee arthroplasty should be fixed to bone with or without bone cement has not yet been definitely answered. We studied movements between the tibial component and bone by radiostereometry (RSA) in total knee replacement (TKR) for 3 different types of fixation: cemented fixation (C-F), uncemented porous fixation (UC-F) and uncemented porous hydroxyapatite fixation (UCHA-F).

Patients 116 patients with osteoarthrosis, who had 146 TKRs, were included in 2 randomized series. The first series included 86 unilateral TKRs stratified into 1 of the 3 types of fixation. The second series included 30 patients who had simultaneous bilateral TKR surgery, and who were stratified into 3 subgroups of pairwise comparisons of the 3 types of fixation.

Results After 5 years 2 knees had been revised, neither of which were due to loosening. 1 UCHA-F knee in the unilateral series showed a large and continuous migration and a poor clinical result, and is a pending failure. The C-F knees rotated and migrated less than UC-F and UCHA-F knees over 5 years. UCHA-F migrated less than UC-F after 1 year.

Interpretation Cementing of the tibial component offers more stable bone-implant contact for 5 years compared to uncemented fixation. When using uncemented components, however, there is evidence that augmenting a porous surface with hydroxyapatite may mean less motion between implant and bone after the initial postoperative year.     

Angiostatic factors normally restrict islet endothelial cell proliferation and migration: implications for islet transplantation

New blood vessel formation in transplanted islets occurs within 7–14 days post-transplantation through both the expansion of donor islet endothelium and ingrowth of blood vessels from the implantation organ. However, several studies indicate that although the islets attract recipient blood vessels, the formed intra-islet vascular network is insufficient, which affects islet post-transplant function. This study aimed to develop an in vitro model to investigate the migration and proliferation properties of isolated liver and islet endothelium. Rat islet or liver endothelium was purified using Bandeiraea simplicifolia (BS-1)-coated Dynabeads. The liver endothelium displayed an increased migration and proliferation to islet-conditioned medium. These effects were fully prevented by adding a neutralizing vascular endothelial growth factor (VEGF)-antibody. In contrast, islet-produced VEGF failed to induce islet endothelial cell migration and only had marginal effects on islet endothelial cell proliferation. These properties could, however, be activated through blocking the effects of either endostatin, thrombospondin-1 or α₁-antitrypsin. In conclusion, VEGF may attract recipient blood vessels towards intrahepatically transplanted islets, but intra-islet vascular expansion is hampered by angiostatic factors present within the islets and the islet endothelium. Inhibition of angiostatic factors early after transplantation may provide a strategy to restore the islet vascular network and improve islet graft function.     

Caerulein-induced pancreatitis and islet blood flow in anesthetized rats

BACKGROUND: Microcirculatory mechanisms have been suggested to be involved in the development of acute pancreatitis. Islet blood flow has not previously been studied in this disease. The present study aimed to investigate the effects of caerulein-induced pancreatitis on pancreatic blood perfusion, especially islet blood flow. MATERIALS AND METHODS: Continuous 4 h caerulein-infusion was used to induce mild, edemateous pancreatitis in anesthetized Sprague-Dawley rats. Some animals were then given an additional 2 h infusion of saline. Thus, at 4 or 6 h after initiating caerulein infusion the blood flow to the pancreas, pancreatic islets, and intestines was measured with a microsphere technique. RESULTS: All infused animals demonstrated an edemateous pancreatitis, without hemorrhages. Both total pancreatic and islet blood flow was increased after the 4-h infusion. However, the increase was less pronounced in the islets. After an additional 2 h with only saline infused, the blood flow values in rats initially infused with caerulein were lower than at 4 h, but total pancreatic blood was still higher than in control rats. No effects on intestinal blood flow values were seen. CONCLUSIONS: Pancreatic islet blood flow in rats with mild edematous pancreatitis is increased, but not to the same extent as that in the whole pancreas.